ArticleMolecular oncology2017
USP22 mediates the multidrug resistance of hepatocellular carcinoma via the SIRT1/AKT/MRP1 signaling pathway.
Article in Molecular oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 105 citations in OpenAlex.
- Roles of ubiquitin‑specific peptidase 22 in cellular fate: From embryonic survival to tissue repair, inflammation and metabolism (Review).International journal of molecular medicine · 2026Review
- Ashwagandha (Withania somnifera) targets liver cancer stem cells via inhibiting Hedgehog signaling pathway in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Article
- Targeting USP22 reprograms the tumor microenvironment and sensitizes KRAS/p53-driven lung cancer to anti-PD-1 immunotherapy.Theranostics · 2026Article
- Molecular regulation by ubiquitin-specific proteases (USPs) in HCC: cell cycle, oncogenic signaling, and beyond.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Therapeutic efficacy of canagliflozin against hepatocarcinogenesis induced by CDD/DEN/TAA in a rat model: regulation of AMPK/HIF-1α/YAP-1/TAZ signaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Review
- A chromatin-focused CRISPR screen identifies USP22 as a barrier to somatic cell reprogramming.Communications biology · 2025Article
- Involvement of SIRT1-mediated aging in liver diseases.Frontiers in cell and developmental biology · 2025Review
- Antineoplastic Activity of Sodium Caseinate in a Cytarabine-Resistant Mouse Acute Myeloid Leukemia Cell Line.Nutrients · 2024Article
- A protein sequence-based deep transfer learning framework for identifying human proteome-wide deubiquitinase-substrate interactions.Nature communications · 2024Article
- MicroRNA-34 and gastrointestinal cancers: a player with big functions.Cancer cell international · 2024Review
- Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.Molecular cancer · 2024Review
- Review
- Role of Ubiquitin-specific Proteases in Hepatocellular Carcinoma Pathogenesis.Current topics in medicinal chemistry · 2024Review
- Phytochemicals as Potential Lead Molecules against Hepatocellular Carcinoma.Current medicinal chemistry · 2024Review
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Article
- Inhibition of USP7 upregulates USP22 and activates its downstream cancer-related signaling pathways in human cancer cells.Cell communication and signaling : CCS · 2023Article
- Potential role of human umbilical cord stem cells-derived exosomes as novel molecular inhibitors of hepatocellular carcinoma growth.Apoptosis : an international journal on programmed cell death · 2023Article
- Contribution of microRNA-30d to the prevention of the thyroid cancer occurrence and progression: mechanism and implications.Apoptosis : an international journal on programmed cell death · 2023Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug treatments for hepatocellular carcinoma (HCC) often fail because of multidrug resistance (MDR). The mechanisms of MDR are complex but cancer stem cells (CSCs), which are able to self-renew and differentiate, have recently been shown to be involved. The deubiquitinating enzyme ubiquitin-specific protease 22 (USP22) is a marker for CSCs. This study aimed to elucidate the role of USP22 in MDR of HCC and the underlying mechanisms. Using in vitro and in vivo assays, we found that modified USP22 levels were responsible for the altered drug-resistant phenotype of BEL7402 and BEL/FU cells. Downregulation of USP22 dramatically inhibited the expression of ABCC1 (encoding MRP1) but weakly influenced ABCB1 (encoding P-glycoprotein). Sirtuin 1 (SIRT1) was reported previously as a functional mediator of USP22 that could promote HCC cell proliferation and enhance resistance to chemotherapy. In this study, USP22 directly interacted with SIRT1 and positively regulated SIRT1 protein expression. Regulation of the expression of both USP22 and SIRT1 markedly affected the AKT pathway and MRP1 expression. Inhibition of the AKT pathway by its specific inhibitor LY294002 resulted in downregulation of MRP1. USP22 and MRP1 expression was detected in 168 clinical HCC samples by immunohistochemical staining, and a firm relationship between USP22 and MRP1 was identified. Together, these results indicate that USP22 could promote the MDR in HCC cells by activating the SIRT1/AKT/MRP1 pathway. USP22 might be a potential target, through which the MDR of HCC in clinical setting could be reversed.
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